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| 1 | Chemokine ligand 2 and paraoxonase-1 in non-alcoholic fatty liver disease:The search for alternative causative factors显示文摘The incidence and prevalence of non-alcoholic fatty liver disease(NAFLD)is constantly increasing.Despite this is apparently associated with the growing increase in obesity,insulin resistance and obesity-related metabolic disturbances their presence is not a necessary or sufficient condition to explain the accumulation of fatin the liver.Conversely,NAFLD is a predictor of other metabolic risks.NAFLD is currently the most frequent chronic liver disease but should not be considered benign or anecdotic because a considerable proportion of patients with NAFLD progress to cirrhosis and endstage liver disease.Consequently,the search for alternative molecular mechanisms with therapeutic implications in NAFLD and associated disorders deserves a careful consideration.Mitochondria are possible targets as these organelles generate energy from nutrient oxidation.Some findings,generated in patients with extreme obesity and in murine models,support the notion that NAFLD could be a mitochondrial disease.This is plausible because mitochondrial dysfunction affects the accumulation of lipids in hepatocytes and promotes lipid peroxidation,the production of reactive oxygen species,the release of cytokines causing inflammation and cell death.Here we discuss basic research and mechanistic studies targeting the role of chemokine ligand 2 in liver inflammation and that of the paraoxonases in the oxidative stress.Their combination and association with mitochondrial dysfunction may uncover mechanisms underlying the progression of NAFLD and may help to identify novel therapeutic targets. | Jordi Camps Jorge Joven | 2015 | World Journal of Gastroenterology2015，21，10： | 4 |
| 2 | Measurement of serum paraoxonase-1 activity in the evaluation of liver function显示文摘Paraoxonase-1 (PON1) is an esterase and lactonase synthesized by the liver and found in the circulation associated with high-density lipoproteins. The physiological function of PON1 seems to be to degrade specific oxidized cholesteryl esters and oxidized phospholipids in lipoproteins and cell membranes. PON1 is, therefore, an antioxidant enzyme. Alterations in circulating PON1 levels have been reported in a variety of diseases involving oxidative stress including chronic liver diseases. Measurement of serum PON1 activity has been proposed as a potential test for the evaluation of liver function. However, this measurement is still restricted to research and has not been extensively applied in routine clinical chemistry laboratories. The reason for this restriction is due to the problem that the substrate commonly used for PON1 measurement, paraoxon, is toxic and unstable. The recent development of new assays with non-toxic substrates makes this proposal closer to a practical development. The present editorial summarizes PON1 biochemistry and function, its involvement with chronic liver impairment, and some aspects related to the measurement of PON1 activity in circulation. | Jordi Camps Judit Marsillach Jorge Joven | 2009 | World Journal of Gastroenterology2009，15，16： | 3 |
| 3 | Liver fat deposition and mitochondrial dysfunction in morbid obesity:An approach combining metabolomics with liver imaging and histology显示文摘AIM: To explore the usefulness of magnetic resonance imaging(MRI) and spectroscopy(MRS) for assessment of non-alcoholic fat liver disease(NAFLD) as compared with liver histological and metabolomics findings. METHODS: Patients undergoing bariatric surgery following procedures involved in laparoscopic sleeve gastrectomy were recruited as a model of obesityinduced NAFLD in an observational, prospective, singlesite, cross-sectional study with a pre-set duration of 1 year. Relevant data were obtained prospectively and surrogates for inflammation, oxidative stress and lipid and glucose metabolism were obtained through standard laboratory measurements. To provide reliable data from MRI and MRS, novel procedures were designed to limit sampling variability and other sources of error using a 1.5T Signa HDx scanner and protocols acquired from the 3D or 2D Fat SAT FIESTA prescription manager. We used our previously described 1H NMRbased metabolomics assays. Data were obtained immediately before surgery and after a 12-mo period including histology of the liver and measurement of metabolites. Values from 1H NMR spectra obtained after surgery were omitted due to technical limitations.RESULTS: MRI data showed excellent correlation with the concentration of liver triglycerides, other hepatic lipid components and the histological assessment, w h i c h e xc l u d e d t h e p r e s e n c e o f n o n-a l c o h o l i c steatohepatitis(NASH). MRI was sufficient to follow up NAFLD in obese patients undergoing bariatric surgery and data suggest usefulness in other clinical situations. The information provided by MRS replicated that obtained by MRI using the-CH3 peak(0.9 ppm), the-CH2- peak(1.3 ppm, mostly triglyceride) and the-CH=CH- peak(2.2 ppm). No patient depicted NASH. After surgery all patients significantly decreased their body weight and steatosis was virtually absent even in patients with previous severe disease. Improvement was also observed in the serum concentrations of selected variables. The most relevant findings using metabolomics indicate increased levels of triglyceride and monounsaturated fatty acids in severe steatosis but those results were accompanied by a significant depletion of diglycerides, polyunsaturated fatty acids, glucose-6-phosphate and the ATP/AMP ratio. Combined data indicated the coordinated action on mitochondrial fat oxidation and glucose transport activity and may support the consideration of NAFLD as a likely mitochondrial disease. This concept may helpto explain the dissociation between excess lipid storage in adipose tissue and NAFLD and may direct the search for plasma biomarkers and novel therapeutic strategies. A limitation of our study is that data were obtained in a relatively low number of patients.CONCLUSION: MRI is sufficient to stage NAFLD in obese patients and to assess the improvement after bariatric surgery. Other data were superfluous for this purpose. | Nahum Calvo Raúl Beltrán-Debón Esther Rodríguez-Gallego Anna Hernández-Aguilera Maria Guirro Roger Mariné-Casadó Lidón Millá Josep M Alegret Fàtima Sabench Daniel del Castillo María Vinaixa Miguelàngel Rodríguez Xavier Correig Roberto García-álvarez Javier A Menendez Jordi Camps Jorge Joven | 2015 | World Journal of Gastroenterology2015，21，24： | 2 |
| 4 | Molecular testing for antibiotic resistance in Helicobactor pylon显示文摘 | R Joven | 2002 | Gut2002，50，3： | 1 |
| 5 | A Key Issue in Production Life Cycle显示文摘 | JOVENE F | 1993 | Annals of CIRP1993，，42： | 1 |
| 6 | Fundamental Differences in Dedifferentiation and Stem Cell Recruitment during Skeletal Muscle Regeneration in Two Salamander Species显示文摘 | Tatiana Sandoval-Guzmán Heng Wang Shahryar Khattak Maritta Schuez Kathleen Roensch Eugeniu Nacu Akira Tazaki Alberto Joven Elly M. Tanaka András Simon | 2013 | Cell Stem Cell2013，，： | 1 |
| 7 | Price Renegotiations in Japanese LNG Contracts Could Lead to a Huge Financial Burden显示文摘 | | 2008 | Gas Insights2008，，110： | 1 |
| 8 | Heterozyous apolipoprotein (a) status and protein expression as a risk factor for premature coronary heart disease显示文摘 | Pedro-Botet J Joven J | 2002 | J Lab Clin Med2002，139，3： | 1 |
| 9 | Immunohistochemical analysis of paraoxonases-1,2, and 3 expression in normal mouse tissues显示文摘 | Marsillach J Mackness B Mackness M Riu F Beltran R Joven J | 2008 | Free Radic Biol Med2008，45，2： | 1 |
| 10 | IFT25 Links the Signal-Dependent Movement of Hedgehog Components to Intraflagellar Transport显示文摘 | Brian T. Keady Rajeev Samtani Kimimasa Tobita Maiko Tsuchya Jovenal T. San Agustin John A. Follit Julie A. Jonassen Ramiah Subramanian Cecilia W. Lo Gregory J. Pazour | 2012 | Developmental Cell2012，，5： | 1 |
| 11 | Increased cutaneous reac-tions to hydroxychloroquine ( Plaquenil) possibly associated withformulation change : comment on the letter by Alarcon 显示文摘 | Salido M Joven B D'Cruz DP | 2002 | Arthritis Rheum2002，46，12： | 1 |
| 12 | The influence of apoprotein (2 homozygosity on nephritic hyperlipidemia显示文摘 | Vilella E | 1997 | Clin Nephrol1997，48，2： | 1 |
| 13 | Plasma protein abnor-malities in nephrotic syndrome: effect on plasma colloidosmotic pressure and viscosity 显示文摘 | Joven J Clivilie X Camps J | 1997 | Clin Chem1997，43，7： | 1 |
| 14 | Abnormalities of lipoprotein metabolism in patients with the nephrotic syndrome 显示文摘 | Joven J Villabona C Vilella E | 1990 | N Engl J Med1990，323，9： | 1 |
| 15 | Transverse myelitis as the first manifestation of systemic lupus erythematosus or lupuslike disease:good functional outcome and rdevance of antiphespholipid antibodies显示文摘 | Mellor-Pita S Joven B | 2004 | J Rheumatol2004，31，2： | 1 |
| 16 | Predictive factors for cutting-out in femoral intramedullary nailing 显示文摘 | Lobo-Escolar A Joven E Iglesias D | 2010 | Injury2010，41，12： | 1 |
| 17 | Changes in the expression of genes related to apoptosis and fibrosis pathways in CCl4-treated rats显示文摘 | Judit Marsillach Natàlia Ferré Jordi Camps Anna Rull Raul Beltran Jorge Joven | 2008 | Molecular and Cellular Biochemistry (-)2008，，1： | 1 |
| 18 | Predictive factors for cutting-out in femoral intramedullary nailing显示文摘 | Lobo-Escolar A Joven E IglesiasD | | 0，，12： | 1 |
| 19 | Immunohistochemical analysis of paraoxonases-1, 2, and 3 expression in normal mouse tissues显示文摘 | Judit Marsillach Bharti Mackness Michael Mackness Francesc Riu Raul Beltrán Jorge Joven Jordi Camps | 2008 | Free Radical Biology and Medicine2008，，2： | 1 |
| 20 | Clinicaloutcomes of minimally invasive versus open approach for one-leveltransforaminal lumbar interbody fusion at the 3- to 4-year follow-up显示文摘 | Rodriguez-Vela J Lobo-Escolar A Joven E | 2013 | Eur Spine J2013，22，： | 1 |
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